Over the past two decades, improved cross-sectional diagnostic imaging techniques have resulted in earlier detection of abnormalities throughout the body. While such non-invasive detection is useful, however, the majority of focal abnormal lesions do not have specific imaging characteristics. For example, lesions smaller than 3 centimeters (cm) often lack specific features to allow reliable noninvasive characterization. Thus, biopsies of focal lesions are often necessary to establish tissue diagnosis of primary or metastatic hepatic malignancy, as well as to perform genotype analysis. Today, percutaneous interventions on focal lesions are among the most commonly performed procedures in Interventional Radiology.
Focal lesion core biopsies are predominantly performed with computed tomography (CT) or ultrasound (US) guidance. However, small lesions can pose several challenges using these techniques. Lesions which are seen on other modalities, such as magnetic resonance imaging (MRI), are sometimes not visible when using CT or US guidance. Alternatively, when the lesion is visible with CT, the biopsy needle introduces beam-hardening artifacts that may render the lesion difficult to see at the critical moment when the needle is in the lesion's vicinity. Furthermore, operator confidence in accurate needle placement using conventional CT or US guidance for biopsies and ablations decreases as target lesions decrease in size. For example, in a study having specialized attending physicians performing liver biopsies, the negative predictive value (NPV) of biopsy for liver lesions less than 3 cm was 72%. Therefore, over a quarter of liver lesions less than 3 cm that had negative biopsies were ultimately proven to be cancerous. It can be reasoned that in a broader community having generalists performing the liver biopsies, the rate of incorrect benign diagnoses would increase.
In light of the above challenges, biopsies are not considered a “perfect” test. In particular, a negative biopsy does not exclude a cancer diagnosis due to the potential for sampling errors. These sampling errors are often caused by: (1) a targeting failure where the core biopsy needle misses the lesion; (2) a sampling failure where the core biopsy needle intersects the lesion, but does not obtain sufficient malignant tissue; or (3) a tumor visualization failure where the tissue section reviewed by a pathologist does not pass through malignancy in the biopsy specimen. Because of these sampling errors, and a present lack of technology for quickly assessing biopsy adequacy, false negative cancer biopsy is very common in clinical cancer care. These errors result in delayed treatment, repeat biopsy procedures, higher costs, increased patient anxiety, and higher risk of biopsy complications.
Various attempts have been made to reduce the rate of false negative biopsy. For example, some institutions perform fine needle aspiration in addition to core biopsy, and then obtain cytologic “wet reads” of fine needle aspirates while the patient is still on the procedure table. This additional step requires on-site cytology specialist expertise, is not widely available, adds considerable procedure and sedation time, cost, and inconvenience, and does not always predict the final biopsy result. Furthermore, cytologic assessment of fine needle aspirate adequacy does not necessarily imply that core biopsy samples will be adequate for the tumor subtyping and genetic analyses necessary to correctly select personalized cancer therapies. Improved image guidance techniques, such as MRI-guided or fusion PET-CT guided biopsies, have also been developed, but these approaches, beyond the added time and cost, are not widely available.
Therefore, there exists a clinical need for a rapid point-of-care technology to assess core biopsy adequacy in a biopsy suite, prior to specimen submission for histopathologic and genetic examinations.